In recent years significant effort has been expended toward developing an immunological approach to contraception. The basic approach has been to either provide an antibody (passive immunization), or to elicit an antibody response (active immunization), to a hormone critical to the establishment and/or maintenance of pregnancy. The production and effects of human chorionic gonadotropin (hCG) in pregnancy have singled out hCG as a prime candidate for studies in immunological contraception. hCG is not present in the normal, healthy female prior to fertilization, but is secreted by the developing blastocyst and can be detected in pregnant women as early as 6 to 7 days after fertilization. hCG, in turn, initially acts upon the corpus luteum, and later upon the placenta, in causing each of them to secrete progesterone. Progesterone, at a high level, acts upon the endometrium to aid in preparing it for implantation and to maintain it after implantation. Therefore, both hCG and progesterone are essential for pregnancy to proceed immediately following fertilization. However, a significant reduction of hCG level prevents sufficient hCG from interacting with the hCG receptors of the corpus luteum and the placenta for maintenance of the high level of progesterone required for pregnancy. Progesterone drops back to or remains at a level too low for support of the endometrium, in the absence of hCG.
A number of researchers have attempted to develop contraceptive vaccines which immunologically block progesterone production. These vaccines provide or produce hCG antibodies to immunologically interact with circulating hCG determinants, thereby preventing the hCG determinants from reaching the hCG receptors of the corpus luteum and of the placenta.
Various problems have prevented commercialization of an hCG vaccine. First, hCG is a human hormone and humans will not normally produce antibody to a human hormone. This problem has been attacked by linking the hCG to a protein such as a hapten. Of course, the hCG antibodies can be produced in normal fashion in animals such as rabbits. However, problems still occur due to the non-specificity of hCG antibody, i.e., high levels of hCG antibody cross react with human luteinizing hormone (hLH); high levels of hCG antibody tend to cause abortion: etc. Low levels of hCG antibodies, which would not cross react with hLH, i.e., are hCG-.beta. specific, were thought to offer the best chance of success, but in practice the circulating life of hCG is extended by formation of loose antigen-antibody complexes.
hCG and hLH, which share common receptors in the gonads as well as follicle stimulatory hormone (FSH), play important roles in the growth of ovarian follicles and in spermatogenesis in the testes.
A group of patents by Bahl (U.S. Pat. No. 4,310,455 and others) concern modification of the .beta. subunit of hCG to produce a more specific hCG antigen for a variety of uses, including a contraceptive vaccine.
U.S. Pat. No. 4,161,519 by Talwar discloses a contraceptive vaccine comprising a purified .beta. subunit of hCG conjugated to an antigen carrier.
A number of papers related to the general subject of contraception based on tying-up circulating hCG are found in Recent Advances in Reproduction and Regulation of Fertility, Elsevier/North Holland, 1977 (G. P. Talwar, Editor), pages 427-485.